Pancreatic regenerative potential of manuka honey evidenced through pancreatic histology and levels of transcription factors in diabetic rat model.

Background: Diabetes mellitus is a commonly occurring metabolic disorder accompanied by high morbidity and alarming mortality. Besides various available therapies, induction of pancreatic regeneration has emerged as a promising strategy for alleviating the damaging effect of diabetes. Honey, a potent antioxidative and anti-inflammatory agent, has been reported in the literature archive to exhibit favourable results in the regeneration process of several organ systems. Design: The current research work was intended to explore the potential role of manuka honey in pancreatic regeneration in alloxan-induced diabetic rats by accessing the pancreatic histology and levels of relevant transcription factors, including MAFA, PDX-1, INS-1, INS-2, NEUROG3, NKX6-1, and NEUROD. An equal number of rats were allocated to all four experimental groups: normal, negative control, positive control, and treatment group. Diabetes was induced in all groups except normal through a single intraperitoneal dose of alloxan monohydrate. No subsequent treatment was given to the negative control group, while the positive control and treatment groups were supplemented with metformin (150 mg/kg/day) and manuka honey (3 g/kg/day), respectively. Results: Statistical comparison of glucose and insulin levels, oxidative stress indicators, changes in the architecture of pancreatic islets, and expression levels of regeneration-associated transcription factors advocated the potential role of manuka honey in ameliorating the alloxan-induced hyperglycaemia, hyperinsulinemia, oxidative stress, and necrotic changes in islets along with significant upregulation of relevant transcription factors. Conclusion: This suggests to us the auspicious role of antioxidants in honey in pancreatic regeneration and advocates the favourable role of manuka honey in combating diabetes mellitus.

Grass-Shaped Zinc Oxide Nanoparticles Synthesized by the Sol-Gel Process and Their Antagonistic Properties towards the Biotrophic Parasite, Meloidogyne incognita.

The presence of Meloidogyne spp., also known as root-knot nematodes, presents a significant danger to global agricultural progress. Since chemical nematicides have high levels of toxicity, it is imperative to develop environmentally friendly methods to manage root-knot nematodes. Nanotechnology is now the most progressive way to attract researchers due to its innovative quality in combating plant diseases. Our study focused on the sol-gel process to synthesize grass-shaped zinc oxide nanoparticles (G-ZnO NPs) and assess its nematicidal behavior against Meloidogyne incognita. Various concentrations (250, 500, 750, and 1000 ppm) of G-ZnO NPs were utilized to expose both the infectious stage (J2s) and egg masses of M. incognita. Laboratory results revealed that G-ZnO NPs showed toxicity to J2s with LC50 values of 1352.96, 969.64, and 621.53 ppm at 12, 24, and 36 hours, respectively, and the result was the inhibition of egg hatching in M. incognita. All three exposure periods were reported linked with the concentration strength of G-ZnO NPs. The pot experiment results exhibited that G-ZnO NPs significantly reduced the root-gall infection of chickpea plants under M. incognita attack. Compared with the untreated control, there was a significant improvement in plant growth attributes and physiological parameters as well, when distinct G-ZnO NP doses (250, 500, 750, and 1000 ppm) were applied. In the pot study, we noticed a reduction in the root-gall index with an increase in the concentration of G-ZnO NPs. The results confirmed that G-ZnO NPs have enormous potential in sustainable agriculture for controlling the root-knot nematode, M. incognita, in chickpea production.

The simultaneous quantification of Sitagliptin and Irbesartan in rat plasma using the validated LC-MS/MS method is applied to a pharmacokinetic study.

Irbesartan (IRB), an angiotensin II receptor AT1 blocker, is an antihypertensive agent commonly used with Sitagliptin (STG), a novel antidiabetic agent in diabetes. A finalised and validated LC-MS/MS method was used for the bioanalytical quantification of STG and IRB to be applicable to studies on the P.K drug-drug interactions between STG and IRB. Using a YMC triart C18 column (50 mm × 4.6 mm i.d., 3 µm), both the drugs and the Tolbutamide were separated using a gradient mode with a flow rate of 1 ml/min with run time of 5 min. For analyte detection, an LC-MS/MS system with multiple reaction monitoring (MRM) was used. The technique was validated across a concentration range of 5-1000 ng/ml, with the LLOQ for both analytes being 5 ng/ml. At all QC levels accuracies from spiked samples were > 83% for both drugs and internal standards. The accuracy for STG within-batch and between-batch was found within 98.4-107.2%, and for IRB was found within 92.4-102.5%. The precision for STG within batch and between batches was less than 12.3% CV, and for IRB was less than 10.2% CV at all concentration levels. The pharmacokinetic profiles of STG and IRB were successfully applied on simultaneous oral administration to rats. This method applies to pharmacokinetic multidrug interaction studies.

Codon Usage Analysis of Pro-Apoptotic Bim Gene Isoforms.

BACKGROUND: Bim is a Bcl-2 homology 3 (BH3)-only proteins, a group of pro-apoptotic proteins involved in physiological and pathological conditions. Both the overexpression and under-expression of Bim protein are associated with the diseased condition, and various isoforms of Bim protein are present with differential apoptotic potential. OBJECTIVE: The present study attempted to envisage the association of various molecular signatures with the codon choices of Bim isoforms. METHODS: Molecular signatures like composition, codon usage, nucleotide skews, the free energy of mRNA transcript, physical properties of proteins, codon adaptation index, relative synonymous codon usage, and dinucleotide odds ratio were determined and analyzed for their associations with codon choices of Bim gene. RESULTS: Skew analysis of the Bim gene indicated the preference of C nucleotide over G, A, and T and preference of G over T and A nucleotides was observed. An increase in C content at the first and third codon position increased gene expression while it decreased at the second codon position. Compositional constraints on nucleotide C at all three codon positions affected gene expression. The analysis revealed an exceptionally high usage of CpC dinucleotide in all the envisaged 31 isoforms of Bim. We correlated it with the requirement of rapid demethylation machinery to fine-tune the Bimgene expression. Also, mutational pressure played a dominant role in shaping codon usage bias in Bim isoforms. CONCLUSION: An exceptionally high usage of CpC dinucleotide in all the envisaged 31 isoforms of Bim indicates a high order selectional force to fine tune Bim gene expression.

Fungal biofilm inhibition by piperazine-sulphonamide linked Schiff bases: Design, synthesis, and biological evaluation.

We report the synthesis of some new piperazine-sulphonamide linked Schiff bases as fungal biofilm inhibitors with antibacterial and antifungal potential. The biofilm inhibition result of Candida albicans proposed that the compounds 6b (IC50 = 32.1 µM) and 6j (IC50 = 31.4 µM) showed higher inhibitory activity than the standard fluconazole (IC50 = 40 µM). Compound 6d (MIC = 26.1 µg/mL) with a chloro group at the para position was found to be the most active antibacterial agent of the series against Bacillus subtilis when compared with the standard ciprofloxacin (MIC = 50 µg/mL). Compound 6j (MIC = 39.6 µg/mL) with an OH group at the ortho position showed more potent antifungal activity as compared to that of the standard fluconazole (IC50 = 50 µM) against C. albicans. Thus, the synthesized compounds 6a-k were found to be potent biofilm inhibitors as well as active antibacterial and antifungal agents. The molecular docking study of the synthesized compounds against the secreted aspartyl protease (SAP5) enzyme of C. albicans exhibited good binding properties. The in silico ADME properties of the synthesized compounds were also analyzed and showed their potential to be developed as potential oral drug candidates.

Comparative anticancer and antimicrobial activity of aerial parts of Acacia salicina, Acacia laeta, Acacia hamulosa and Acacia tortilis grown in Saudi Arabia.

The standardized ethanol extract (EE) of aerial parts of four Acacia species [A. salicina (ASEE), A. laeta (ALEE), A. hamulosa (AHEE), and A. tortilis (ATEE)] were examined in order to compare their cytotoxic and antimicrobial activities. All the extracts were standardized by UPLC- PDA method using rutin as standard compound. The extracts ALEE, AHEE and ATEE were found to contain rutin along with several other phytoconstituents while rutin was absent in ASEE. All the extracts showed varying level of antimicrobial activity with zone of inhibition ranged from 11 to 21 mm against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. The ALEE and ATEE showed relatively high antimicrobial potency (MIC = 0.2 to 1.6 mg mL-1) in comparison to other extracts. All the extracts were found to reduce the biofilm of P. aeruginosa PAO1 strain significantly in comparison to the untreated control. The cytotoxic property of ASEE, ALEE, AHEE, ATEE were evaluated against HepG2 (Liver), HEK-293 (Kidney), MCF-7 (Breast) and MDA-MB 231 (Breast) cancer cells. Of these, ALEE, AHEE and ATEE exhibited moderate cytotoxic property against human liver carcinoma cells (HepG2; IC50 = 46.2, 39.2 and 42.3 µg mL-1, respectively) and breast cancer cell lines (MCF-7; IC50 = 57.2, 55.3 and 65.7 µg mL-1, respectively). The ATEE and ALEE showed moderate cytotoxicity against HEK-293 (kidney) cells with IC50 = 49.1 and 53.5 µg mL-1, respectively. Since, Acacia species (A. laeta and A. hamulosa) contains numerous polyphenols which might prove to be highly cytotoxic and antimicrobial agents, we suggest that these species can be further subjected to the isolation of more cytotoxic and antimicrobial compounds.